1. Field of the Invention
The present invention relates to an electrolyte solution used in an electrical or optical particle measuring apparatus. More specifically, it relates to an electrolyte solution comprising an organic solvent as the solvent.
2. Related Art
It is common to conduct measurement of the numbers and sizes of different types of particles of cells in blood or urine samples or of fine ceramics, pigments, toners and the like. Such particle measurement has been achieved based on optical or electric measuring principles.
One example of an optical method is the method in which: a sample containing the particles to be measured is continuously fed through a flow cell, the flow cell is irradiated with laser light, and optical information such as scattered light or fluorescent light is obtained to detect the presence of the particles or the sizes of the particles. Another example entails imaging particles in a flow cell with a video camera and analyzing the image.
Various optical measuring apparatuses for automatic measurement of particles by such optical methods are proposed in U.S. Pat. No. 5,325,168, U.S. Pat. No. 5,325,169 and U.S. Pat. No. 5,721,433, and elsewhere.
On the other hand, electrical particle measuring methods generate information about particles by means of an orifice between electrodes through which a current flows. A sample solution containing the particles is passed through the orifice and the change in impedance between the electrodes is detected as the particles pass through the orifice. In one such electrical method, the particles are passed through an orifice in which a direct current flows, and the change in impedance is obtained as a pulse signal. The degree of change in the pulse signal differs depending on the sizes (volumes) of the particles.
In another electrical method, the particles are passed through the orifice through which a high frequency current flows, and the change in impedance is obtained as a pulse signal. When high density portion sand low density portions are present in a single particle, the impedance of each for the high frequency current will differ, and therefore internal information on the particles can be obtained. For example, it is possible to obtain information on the sizes and density of the nuclei in cells such as leukocytes.
Various apparatuses for automatic measurement of particles by such electrical methods are proposed in U.S. Pat. No. 3,444,463, U.S. Pat. No. 3,444,464, U.S. Pat. No. 5,274,431, and elsewhere. These apparatuses, however, often exhibit problems including: the detection signal differs depending on the position at which the particles pass through the orifice, multiple particles sometimes pass through the orifice in close proximity and are measured as a single particle, or particles that have passed through the pore accumulate around the orifice and flow backward, creating noise. In order to solve these problems, a sheath flow system is often used in combination therewith.
In a sheath flow system, the sample solution containing the particles is surrounded by a sheath solution before passing through the orifice. This solves the aforementioned problem because the sample solution is hydrodynamically constricted at the center of the sheath solution flowing, in a laminar flow state (“sheath flow”), and the particles therefore pass through the orifice in a highly precise single file. Sheath flow systems are also widely used for optical particle measuring apparatuses. They allow continuous feeding of particles in a precise manner in a limited detection zone.
In an electrical particle measuring apparatus, the orifice and electrodes must be filled with the electrolyte solution at the time of measurement. That is, the sample solution, i.e., the dispersion medium for dispersion of the particles (hereafter “dispersion medium”), and the sheath solution must be electrolyte solutions.
The solvent used for the electrolyte solution is most commonly water. This is because dissolution of a salt such as sodium chloride in the water provides electrolyte solutions with the electric conductivity required for particle measurement. Since the measurement is preferably carried out without affecting the sizes or shapes of the particles, a saline solution containing a buffer or preservative is usually used for measurement of cells such as blood cells. For example, Japanese Unexamined Patent Publication SHO No. 52-58993, Japanese Examined Patent Publication HEI No. 1-33780 and Japanese Examined Patent Publication HEI No.3-27865 disclose diluents for electrical particle measuring apparatuses using water as the solvent. Japanese Unexamined Patent Publication HEI No. 10-160730 discloses the use of buffered saline in an impedance transducer cell analyzer for count and size sorting of erythrocytes and platelets.
However, when the objects of measurement are water-soluble particles such as ingestible drugs or foods, detergent granules, or certain pigments, water cannot be used as the solvent for the electrolyte solution. That is because the particles dissolve, making it difficult to accurately measure the numbers and sizes of the particles.
Moreover, depending on the type of particles to be measured, using water as the solvent for the electrolyte solution can cause aggregation. Therefore, water is not preferred as the solvent of the electrolyte solution for certain types of particles. Aggregation of the particles makes it difficult to accurately measure the numbers and sizes of the particles.
In such cases, therefore, particle measurement requires an organic solvent as the electrolyte solution solvent, instead of water. But since organic solvents exhibit almost no electric conductivity, the use of an organic solvent requires dissolution of some type of salt in the solution to provide the conductivity necessary for particle measurement.
The types of salts that dissolve in organic solvents are limited. However, it is known that the inorganic salts lithium chloride and lithium perchlorate dissolve in organic solvents. Accordingly, solutions of lithium perchlorate in organic solvents such as methanol or isopropanol have been used as electrolyte solutions to increase electric conductivity in electrical particle measuring apparatuses.
However, lithium chloride and lithium perchlorate accelerate corrosion of the apparatuses. This suggests using inorganic salts other than lithium chloride and lithium perchlorate, for example, sodium chloride or calcium chloride. However, inorganic salts such as sodium chloride are less soluble in organic solvents than in water, and it has therefore been difficult to increase conductivity enough to allow particle measurement.
Organic salts such as sodium acetate or sodium citrate are also known to dissolve satisfactorily in organic solvents such as methanol and thereby increase conductivity. However, organic salts tend to cause the particles to aggregate, which hinders measurement of the particle size distribution.
On the other hand, organic solvents have conventionally been used in dispersion media or sheath solutions for optical particle measurement. Unlike with electrical particle measurement, there is no need to increase the conductivity of the organic solvent. However, when the dispersion medium or sheath solution contains such an organic solvent, it can only be used for optical particle measurement and not for electrical particle measurement.